Method of manufacturing alpha-alpha-diaminopyridine



' at a temperatureof about 350 (3., untilno Patented Jan. 13, 1931 UNITED STATES OF NEW YORK; N. Y-, A CORPORATTON YORK KARL PHILIPP, or YONKERS, NEW YORK, nssicnonfrornn'rynrnruivr 'ooaroitnrronf METHOD or MANU ACTURING ALrHmALrnn-msiumorrnrmnn I 1T0 Drawing.

This invention is an improvement in methods of manufacturing apha-alpha-diaminopyridine. V

The usual method of manufacturing alphaalpha-diaminopyridine, contemplates two distinct steps, the first being the obtaining of sodamide, and the second the reacting of the sodamide with pyridine.

Sodamide is produced by treating fused sodium metal with dry ammonia gas, usually by bubbling the gas through the fused metal unchanged metal'is visible on the surface of the melt.

The sodamide consolidates on cooling into a hard mass, and from this state it must be transformed into a condition of loose molecular cohesion in order to react it' with the pyridine. This condition is produced by fusion, or by mechanical pulverization, and be cause of the atfinity of the sodamide for water, the pulverization must take place in a dry atmosphere.

After pulverization, the sodamide and pyridine are mixed in a medium which is chemically indifferent to sodamide (NaNH pyridine, and alpha-alpha-diaminopyridine, and which from a physical point of View possesses the requirements'as a medium for the reaction. Oil media, such as Russian oil, dimethylaniline and diethylaniline have been used. Naphthalene and potassium cyanide are also suitable for the purpose. All of these media are objectionable,-however, in that they form an impurity after the cessation of the amido forming, and after the alpha alpha diaminopyridine is isolated. This impurity must be. eliminated, which resulted in the slowing up of theprocess, and increase in the cost of the product.

In the usual process, the dry pyridine is added to the sodamide pulverized or emulsified with the medium, (diethylaniline mineral oil, or the like). Hydrogen is freed in the reaction, and the sodium compound of alphaalpha diaminopyridine is formed, which is afterwards transformed into the free diamino product and sodium hydroxide, by the careful addition of water. Or carbonic acid may be used (in which case sodium car- Application filed se teiiiter 30,1927. Serial no. 223,242.

bona't ef; freed :diamind-pyridine are formed. The productionfresults, however,

are mediocre, since any impurity greatly re-.,

duces the yield. When water is used the caus-' tic so da produced oxidizes a part ofthe amino pyridine, and this is lost asan impurity..-

I Investigation disclosedsthat the production of alpha-alpha-diaminopyridine increased in accordance with diminution ofthe reaction 7 medium, when the reaction was carried on at a relativelyhhigh temperature. The in-- crease ofthe desired productadvanced with f diminution of the reaction medium from about 40.- -50.% to 80% of thetheoretical amount, w ith 1 a product of 7 much greater purity.

By increasing the. temperature ofthe soda l mide at the beginningof the, reaction, I am able .to entirely. eliminate the reaction me dium, which is the" cause of the, impurities,

and tovery greatly increase the yield, of a v I relatively; purezproduct, thus eliminatingthe necessity for the troublesome pulv'erization oremulsificationof the sodamide. i

One of the primary objects or the present invention is the provision of a method where by a substantially pure product may be obtained. 1 a 1 Another object is the provision of a method enabling the directv coupling of the pyridine .80 with the sodamide, without the interposition ofa neutral medium, thus to provide-a prod-' uct'nwith no 'admixture of, substances other than those directly resulting from the reaction. .7

In carrying out the process, a retort is provided, equipped with a stirring apparatus, and means enabling a continuous flow of dry ammonia gas to the'bottom of the res tortl The retort should also. be of a nature such that a pressure of from 4 to 5 atmos pheres may be maintained therein.

Asuitable quantity of metallic sodium is 'placed'inithe retort, and brought gradually to a temperature'of about 400 C, under a pressure of about 4 to 5 atmospheres, and with vigorous agitation. The dry ammonia gas isconducted through the meltv during the raising of the temperature, and in from 4 tohours all of the metal is converted into sodamide. i

The sodamide is then cooled to a temper ature somewhat above its melting point, that 5 is about 220C.,and dry pyridine is added very slowly and carefullyvwith continuous stirringor agitation. lVhilehydrogen is be; ing freed in the'reaction, a considerable agitation results, and after some time the prodw uct in the retort will form a solid mass which can no longer be stirred or agitated. The; temperature isheld at about from 200 to V 210 C., as long asany hydrogen escapes, and

the process is completed in about 12 to 15 15 hours. V

The product is'tlie disodium compound of alpha-alpha-diaminopyridine, and this is. transformed into free alpha-alpha diaminopyridine, and NaOH or Na CO by the'slow introduction of cold water or carbonic acid gas as the case may be, it being understood that'either may be used. The raw mass is then dissolved in'suflicient hot water, and filtered; While stirring and cooling, the alpha-alpha-diaminopyridine is separated with sodium hydroxide and sodium chloride. Further purification can be obtained if desired by recrystallizing from benzene, toluene or Xylene. The improved process greatly simplifies the manufacture of alpha-alpha-diaminopyridine in that the reaction between the py'ri-- dine and the melted sodamide is direct, and prior pulverization or emulsification of the sodamide with a reaction medium is eliminated. No supplemental purification of the diamino product is required, as would be the case werea neutral reaction medium used, since with the use of such media they must be removed from the product. No special construction of apparatus is'nece ssary, and the'production costs of the alpha-alpha-diaminopyridine are considerably reduced.

What is claimed as new is 1. The method of obtaining alpha-alphadiaminopyridine, which consists in the direct addition of pyridine to sodamide while the sodamide is in a state of fusion.

2. Themethod of obtaining alpha-alphadiaminopyridine, which consists in the di- .,rect addition of pyridine to sodamidewhile the sodamide is in a state of fusion at a temperature of about 220 C.

3. The method of obtaining alpha-a1phadiaminopyridine, which consists in the di rect addition of pyridine to sodamide While the sodamideis in a state of fusion, and con- .verting the product into free alpha-alphadiaminopyridine and a sodium salt. Signed at New York city, in the county pof New York and State of New York this 29th day of Sept, A. D. 1927.

V KARL PHILIPP. 

